Inhibitory effect of almitrine on dopaminergic activity of rat carotid body

Abstract

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.

Pattern of breathing and laryngeal patency following almitrine bismesylate in anesthetized cats

“…Consistent with previously reported increases in tidal volume following almitrine administration [4,7,8,9,17], we found an increase in ventilatory flow rate. The substantial increase in inspiratory airflow induced by almitrine seems to depend to a large extent on the integrity of the vagus nerves.…”

“…Minute ventilation in rats with normal initial blood gas-tension generally increased after doses in the range 1-20 mg/kg, with little variation in response in this dose range, and with no improvement in arterial oxygenation [4]. Pequignot et al [17], using the dose of 5mg/kg (administered intraperitoneally) on untreated rats, described a consistent improvement in PaO2. It is possible that a larger dose of almitrine could improve the arterial oxygen tension in cats [14].…”

Differential effects of ventilatory stimulation by sex hormones and almitrine on hypoxic erythrocytosis

“…Several lines of evidence indicate that almitrine acts by specifically stimulating the peripheral arterial (carotid body) chemoreceptors [13,23]. In agreement with a previous study [23], the present data confirmed that, like the progesterone plus estrogen treatment, almitrine inhibits the catecholamine activity in the carotid body. Almitrine did not alter the catecholamine content, thus indicating that almitrine inhibited both the release and synthesis of catecholamines to a similar extent.…”

“…Thus, progesterone, which is known to be a potent and chronically effective ventilatory stimulant [5,27], has been shown to decrease Ht [11]. On the other hand, almitrine, which stimulates arterial chemoreceptors specifically [13,23], was also found to reduce Ht, although to a lesser extent [29]. However, in both studies [11,29], the precise mechanisms involved in the effectiveness of the drug therapy were not elucidated, but could be linked either to a central or a peripheral action of the drugs on ventilation.…”

“…These brainstem catecholaminergic neurons are target sites for sex steroid hormones [8] and the close anatomical interrelations between steroid receptors and catecholaminergic neurons are thought to play a significant role in the regulation of a number of physiological processes [8]. On the other hand, it has been shown that almitrine has an effect on catecholaminergic activity in the rat carotid body [23] and on respiratory neurons of the NTS [14].…”